This post subtitles: 2 Steps, 1 Leap
Hopkins, I’d call him Hoppy, was an old-fashioned chemist. Which was to say that his all seasons brown suit, check shirt and braces belonged more in the plant offices of industrial chemical processing than sharp new organic and biological laboratories. But Guinness liked him and his respectable cut held more for their North London venture’s management than any of the new crowd. From PM Wilson’s scientific future flock.
A quantitative professional, measure to his mind superior to mere chemical presence. And the reason he sat behind his desk in a corner of the second floor premise. North of Western Avenue and Walls sausages where, gossip held, a future Maggie Thatcher had commenced minion career in an experimental ice-cream shack.
In his room without a view Hoppy acquired a crafty skill. Rather than admit ignorance he would nod. I was to term it the not-nod. Not for him an understanding of novel gas chromatography to separate small volumes of fats. Not for him my nouveau recollections of titrating hydrofluoric acid in I.C.I. fume cupboards. Hairs rose on the back of necks at such exploits, but if they did with Hoppy it was lost to the nod. At the job interview so fascinated was I with it that I missed the look in his eyes at relating my ambition to make better iron absorption possible for anaemic patients.
Thusly I was surprised to receive an interim job offer several weeks later. Just back from my first OE and pretty broke I took it. To realise how his ignorance was my gain in having a free hand to R&D inorganic iron onto saccharide(sugar) transfer complexes. The one haematinics option of its time and place to gain a good look. And soon resulting in healthier and bigger pigs.
Hoppy smiled more, doubtless thrilled with his office’s well-taken praise from firm overseers and management. Pork, bacon and foods market revenues were well worth having in addition to their excellent beverage as Europe recovered and its populations began to bulge. Besides which patented properties accrued for their holders both across the Atlantic and later the world. Big business indeed, as Virginia’s joy - - in recent days has shown.
Smiling, however, does not make the vet-lit and the past was to resettle on Hoppy as soon as I’d left to pursue med-lit mentions for myself. Plus salting away any spare cash I could muster at evening dinner tables - eat your heart Abel* - into sure things.
Yet to Hoppy I am impelled to attribute a very solid lesson regarding parental administration of chemical substances. In short: WHAT GOES IN HAS GOT TO COME OUT. And no, not as a bloody rash at the site of injection! As he put it so very well.
* Protagonist in the novel Kane & Abel.
Step UP
In relating that small step back I believe readers are more able to register several aspects of last week’s post ( qv below ). And in returning to chloramphenicol for what it was capable of inside the body of a patient for whom aplastic anaemia was never intended.
Better is Miller Keanes’s Medical dictionary— aplastic [a-plas´tik] - pertaining to or characterized by aplasia( = bone marrow failure); having no tendency to develop into new tissue…[ note: with my underlining ] This may be due to:—
- chemical factors such as drugs,
- physical factors such as radiation,
- infection by a virus, or
- idiopathic congenital defects of the stem cells of the bone marrow.
Added to which - and relating to upcoming content on the treatment for PNH mentioned earlier - I’d like to widen context of recorded findings in respect of contemporary doctors checking the immune system for proteins called antibodies. They say, “Antibodies in the immune system that attack your bone marrow cells may cause aplastic anemia.”
What was it about this inexpensive, rapidly absorbed and distributed bacteriostatic (inhibits bacteria as distinct from bactericides which kill) antibiotic whose 250mg capsules were easily taken by mouth..?
Relative that is to aplastic anaemia's(AA) rarity. Back in the day, 1 case in 50K, was held to be the U.K. incidence. That is 1 case in 50K chloramphenicol courses of treatment. Hardly noticeable you might conclude correctly. In fact twas some 3 years from its introduction before serious blood disorders were reported. Recipe for rarity was large city populations, widespread prescribing and broad spectrum application. Thence to children, in whom a greater and closer parental scrutiny was I daresay taken.
But this rarity in reality was part of the problem. Witness Gairdner’s case (BMJ, 1954, 2, 1107). “A girl of 4 years” presenting “on attack of bronchitis and asthma for which she received 1gm daily for 4 days. Six months later she developed a sore throat, treated with a further course of 1gm daily for 4 days. Three days after completing this course a purpuric(blood) rash appeared and in spite of blood transfusion she died two weeks later”. AA was found at necropsy.
Suggests, does it not, how the first course whilst presumably working also found and ‘occupied’ a vulnerability in the patient’s body. Made worse and much more obviously SIX MONTHS LATER!
Bringing us back to the question of what was going on inside the patient?
Answers came after a fairly brutal trial in premature babies. At the time routine chemoprophylaxis(antibiotic cover) was prevalent. [ Recall if you will the 1920s period Downton Abbey drama whereby watchers saw the medical debate around Lady Sybil’s delivery. Caesarean, they argued, could kill both mother and child—we have no treatments to use—].
3 decades on the trial allocated 4 treatment groups of approx. 30 babies each:—
- no drug,
- chloramphenicol(C),
- penicillin(P) + streptomycin(S), and
- P + S + C.
Cause of death was circulatory collapse with high chloramphenicol plasma concentrations due to a failure of the liver to conjugate, and kidney to excrete, the drug.
What WAS GOING IN WAS STAYING IN. Not changing, as with older and competant organ development, but damaging by its continued presence.
Yes, biochemical investigation in the fate of drugs in the IMMATURE can predict safe dosage schedules, but point is made that UNCONTROLLED chemoprophylaxis with its loss of life is not to be tolerated by clinicians.
Indeed uncontrolled anywhere, anytime and over time is to be avoided wherever possible.
Leap.
Fifty years + later I was to see an aging lady with one very swollen and angry toe. No, she recalled to her doctor’s question, she had not “banged” it in the garden. Yet ohh.. hadn’t she stubbed it on a bedpost. He stooped, leaned, looked, felt then washed his hands. Talking all the while to put her mind at ease.
“Classic case.. you ask me.. You are asking me aren’t you.. thought so.. and for classic cases - I’d take a photo if I hadn’t seen so many like it in my time. Yes, you’re bigger than many but not so big that my classic treatment with its life of efficacy wont polish it orf in next to no time… Now quiet please while I get this newfangled computer to print out your very own prescription..”
In thrall she pulled a large stocking back over her foot and took the print out with her. As I looked at the screen in some astonishment.
“Well, said he to me with a grin, “some of your questions I can’t answer—too special for a GP like me, but I know gout when I see it and… and I do know how to treat it. Stubbed it, came up real fast right.. I say Staph aureus.. and that’s how you deal with it. Do you know the people who make this antiobiotic held it back for years.. and years. Keep it in your bag, doc, their rep would tell me, you never know when.. blah blah. What’s funny, whaddya smiling like that for..?”
“Life of efficacy,” I said. And he grinned again. Then, not wishing to explain himself, said, “ This time tomorrow she’ll be right. But I must get nurse to call and make sure she finishes the course.”
And she was, and she did. Erythromycin had made the leap.
